Phase 1/Expansion Study of Tazemetostat Plus Belinostat for the Treatment of Relapsed or Refractory Lymphoma

Status: Recruiting
Location: See all (11) locations...
Intervention Type: Drug, Procedure, Other
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This phase I trial tests the safety, side effects, and best dose of combination therapy with tazemetostat and belinostat in treating patients with lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Tazemetostat is in a class of medications called EZH2 inhibitors. The EZH2 gene provides instructions for making a type of enzyme called histone methyltransferase which is involved in gene expression and cell division. Blocking EZH2 may help keep cancer cells from growing. Belinostat is in a class of medications called histone deacetylase inhibitors. Histone deacetylases are enzymes needed for cell division. Belinostat may kill cancer cells by blocking histone deacetylase. It may also prevent the growth of new blood vessels that tumors need to grow and may help make cancer cells easier to kill with other anticancer drugs. There is some evidence in animals and in living human cells that combination therapy with tazemetostat and belinostat can shrink or stabilize cancer, but it is not known whether this will happen in people. This trial may help doctors learn more about treatment of patients with relapsed or refractory lymphoma.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• DOSE ESCALATION PHASE: Patients with relapsed or refractory non-Hodgkin lymphoma including both B-cell non-Hodgkin lymphoma (NHL) and T-cell NHL. Refractory cutaneous T-cell lymphoma (CTCL) will be allowed if greater or equal to stage 1B and have previously failed two systemic therapies

• DOSE EXPANSION PHASE: Patients with relapsed or refractory follicular, transformed lymphoma or germinal center B-cell diffuse large B-cell Lymphoma (GCB-DLBCL) as defined by Hans criteria, as well as T-cell lymphomas. For patients with B-cell lymphomas, equal numbers of patients will be enrolled onto one of 2 arms: (1) mutated EZH2 or (2) wild-type EZH2. EZH2 mutations will be identified by polymerase chain reaction (PCR)

• Patients must not be eligible for, or have refused, stem cell transplantation or chimeric antigen receptor T-cell (CAR T-cell) therapy

• Patients who have undergone 1-5 prior treatments of any type (progression after transplant/cellular therapy allowed) are eligible

• Patients must have measurable disease according to the Lugano classification

• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of tazemetostat in combination with belinostat in patients \< 18 years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

• Absolute neutrophil count \>= 1,000/mcL

⁃ If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants should have: absolute neutrophil count (ANC) \>= 0.75 × 10\^9/L

• Platelets \>= 75,000/mcL

⁃ If there is documented lymphomatous involvement of the bone marrow as assessed by bone marrow biopsy within 90 days prior to registration, participants should have: platelets \>= 50 x 10\^9/L

• Total bilirubin =\< 1.5 institutional upper limit of normal (ULN); unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver, in which case total bilirubin should be =\< 5 x institutional ULN

• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN; unless due to Gilbert's disease, hemolysis, or lymphomatous involvement of liver, in which case AST(SGOT)/ALT(SGPT) should be =\< 5 x institutional ULN

• Glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients whose lymphoma has transformed from a less aggressive histology remain eligible

• Patients should be New York Heart Association Functional Classification of class II or better

• Patients must have a QT interval corrected by Fridericia's formula (QTcF) =\< 450 msec

• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels

• The effects of tazemetostat and belinostat on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use two reliable methods of contraception simultaneously prior to study entry and for the duration of study participation and for 6 months after the last dose of the study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of tazemetostat and belinostat administration. Male participants must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation

• Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible

• Patients that have received prior chemotherapy or radiotherapy must have completed their last treatment at least 2 weeks before entering the study. Rituximab given between EZH2 analysis and initiation of study drugs will be allowed

Locations
United States
California
University of California Davis Comprehensive Cancer Center
RECRUITING
Sacramento
Connecticut
Yale University
RECRUITING
New Haven
Kansas
University of Kansas Clinical Research Center
RECRUITING
Fairway
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
New Jersey
Rutgers Cancer Institute of New Jersey
RECRUITING
New Brunswick
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
Ohio
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Virginia
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Time Frame
Start Date: 2023-03-01
Estimated Completion Date: 2026-09-01
Participants
Target number of participants: 48
Treatments
Experimental: Treatment (tazemetostat, belinostat)
Patients receive tazemetostat PO BID on days 2-21 of cycle 1 and days 1-21 of subsequent cycles, and belinostat IV over 30-180 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.~Patients may undergo a tumor biopsy during screening and on study (dose-expansion only). Patients undergo blood sample collection while on study and CT or PET/CT scan throughout the study.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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